title: Design of tablets for the delayed and complete release of poorly water-soluble weak base drugs using SBE7M-β-CD as a solubilizing agent.
abstract: The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66046. venkatramana.rao@bms.com.
authors.forename: Venkatramana M
authors.initials: VM
authors.lastname: Rao
authors.forename: Erika A
authors.initials: EA
authors.lastname: Zannou
authors.forename: Valentino J
authors.initials: VJ
authors.lastname: Stella
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D009995:Osmosis; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D013608:Tablets, Enteric-Coated; D047392:beta-Cyclodextrins; D014867:Water
keywords: Complexation; Controlled release; Cyclodextrins; Delayed release; Osmosis; Diffusion; Enteric polymer; Solubility